The U.S. Department of Health and Human Services (HHS) guidelines recommend that HIV infected patients who have never received anti-HIV therapy be treated with a triple drug regimen. The most commonly prescribed and successful regimen contains the medication efavirenz (EFV). However, this regimen may not be an option for everyone, hence alternative regimens are needed.

This study was designed to look at how well different combinations of anti-HIV drugs work to decrease the amount of HIV in the blood (viral load) of and allow immune system recovery in people who have never received anti-HIV therapy. This study also examined drug tolerability and safety for the various drug combinations.

Cumulative Probability of First Virologic Failure by Week 96 [ Time Frame: From study entry to week 96 ] [ Designated as safety issue: No ]

The Kaplan-Meier estimate of the cumulative probability of virologic failure by week 96.

Time to virologic failure was defined as the first time from study entry to the first of two consecutive HIV-1 RNA >1000 copies/mL at or after week 16 and before week 24, or >200 copies/mL at or after week 24. Week 16 is defined to occur between 14 (98 days) and 18 weeks (126 days) after study entry, week 24 is defined to occur between 22 (154 days) and 26 (182 days) after study entry, and week 96 is defined to occur between 88 (616 days) and 104 (728 days) after study entry.

Cumulative Incidence of Discontinuation of the RAL or PI Component of Randomized Treatment for Toxicity by Week 96 [ Time Frame: From study entry to week 96 ] [ Designated as safety issue: No ]

The cumulative incidence of discontinuation for toxicity by week 96 was estimated using competing risks with treatment discontinuation for other reasons considered as a competing event; participants completing the study on the RAL or PI component of their randomized regimen were considered censored at the earliest of the date of last patient contact and off study date.

The cumulative incidence of first adverse event (with and without total bilirubin and creatine kinase and measured from study entry) by week 96 was estimated using methods for competing risks. Discontinuation of randomized treatment prior to an adverse event was considered a competing event.

The time to the first of any post-entry Grade 2, 3, or 4 sign or symptom, or Grade 3 or 4 laboratory abnormality while on randomization. The protocol required reporting of signs and symptoms and laboratory values as follow: all signs and symptoms grade ≥2 post-entry to week 48, signs and symptoms grade >3 after week 48, and laboratory values grade >3 and all signs, symptoms, and laboratory values that led to a change in treatment, regardless of grade throughout out all post-entry follow-up.

Cumulative Probability of Time to Loss of Virologic Response (TLOVR) by Week 96 [ Time Frame: From study entry to week 96 ] [ Designated as safety issue: No ]

The Kaplan-Meier estimate of the cumulative probability of TROVR by week 96.

If participants never achieved a confirmed HIV-1 RNA≤200 cp/mL (on two consecutive visits) prior to death, permanent discontinuation of randomized treatment, or time of last available HIV-1 RNA evaluation, TLOVR was equal to 0; otherwise, TLOVR was the earliest time of permanent discontinuation of randomized treatment prior to study close-out period, time to confirmed levels >200 cp/mL, or time to death. If TLOVR is immediately preceded by a single missing scheduled visit or multiple consecutive missing scheduled visits, TLOVR is replaced by the first such missing visit.

Presence of Mutations Associated With NRTI Resistance [ Time Frame: At the virologic failure at any time throughout the study (up to 213 weeks) ] [ Designated as safety issue: No ]

The number of participants with NRTI resistance determined by the Stanford resistance scoring algorithm (Version 6.3). All sequencing was performed regardless of status on randomized treatment at the time of virologic failure; no sequencing was performed on subjects not meeting virologic failure.

Presence of Mutations Associated With ATV/RTV or DRV/RTV Resistance [ Time Frame: At the virologic failure at any time throughout the study (up to 213 weeks) ] [ Designated as safety issue: No ]

The number of participants with ATV/RTV or DRV/RTV resistance determined by the Stanford resistance scoring algorithm (Version 6.3). All sequencing was performed regardless of status on randomized treatment at the time of virologic failure; no sequencing was performed on subjects not meeting virologic failure.

Presence of Mutations Associated With INI Resistance [ Time Frame: At the virologic failure at any time throughout the study (up to 213 weeks) ] [ Designated as safety issue: No ]

The number of participants with INI resistance determined by the Stanford resistance scoring algorithm (Version 6.3). All sequencing was performed regardless of status on randomized treatment at the time of virologic failure; no sequencing was performed on subjects not meeting virologic failure.

Incidence of Death or AIDS Defining Events (CDC Category C) [ Time Frame: Study entry to off-study at any time throughout the study (up to 213 weeks), participant follow-up time was variable ] [ Designated as safety issue: Yes ]

The incidence of death or AIDS defining events (CDC category C) was estimated as number of incident events over total person years of follow-up. Multiple new events for a single subject were counted toward events totals in estimation of event incidence; generalized estimating equations were used to estimation of robust standard errors for the incidence.

The incidence of targeted serious non-AIDS defining events was estimated as number of incident events over total person years of follow-up. Multiple new events for a single subject were counted toward events totals in estimation of event incidence; generalized estimating equations were used to estimation of robust standard errors for the incidence.

Only fasting results are included. Change was calculated as the fasting plasma glucose at week (48, 96, and 144) minus the baseline fasting plasma glucose.

Change in Framingham 10-year Risk of MI or Coronary Death From Baseline [ Time Frame: Study entry to weeks 48, 96, and 144 ] [ Designated as safety issue: No ]

Only risk score estimated with fasting lipid results were included. Change was calculated as the Framingham 10-year risk of MI or coronary death at week (48, 96, and 144) minus the baseline Framingham 10-year risk of MI or coronary death. Framingham 10-year risk of MI or coronary death was calculated using Hear Coronary Heart Disease (10-year risk) found at https://www.framinghamheartstudy.org/risk-functions/coronary-heart-disease/hard-10-year-risk.php.

Framingham 10-year risk of MI or coronary death was calculated according to age, laboratory values of total cholesterol and HDL cholesterol, smoking status, systolic blood pressure, and treatment for hypertension. The Framingham 10-year risk of MI or coronary death was calculated as: for males: <0 point (<1 percent risk) up to ≥17 points (≥30 percent risk); whereas for females: <9 points (<1 percent risk) up to ≥25 points (≥30 percent risk). Higher scores indicate high cardiovascular risk.

No evidence of any exclusionary mutations defined as any major NRTI or PI resistance-associated mutation on any genotype or evidence of significant NRTI or PI resistance on any phenotype performed at any time prior to study entry. NNRTI-associated resistance mutations are not excluded. More information on this criterion can be found in the study protocol.

No prior anti-HIV therapy. More information on this criterion can be found in the study protocol.

Viral load is 1000 copies/mL or higher, as measured within 90 days prior to study entry

Participating in research at any AIDS Clinical Trial Group (ACTG) clinical research site or select International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group sites

Ability and willingness of subject or legal guardian/representative to give written informed consent

Exclusion Criteria:

Use of immunomodulators, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. Those using stable physiologic glucocorticoid doses, a short course of pharmacologic glucocorticoid, corticosteroids for acute therapy treating an opportunistic infection, inhaled or topical corticosteroids, or granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) will not be excluded.

Known allergy or sensitivity to study drugs or their ingredients. A history of sulfa allergy is not excluded.

Any condition that, in the opinion of the investigator, would compromise the participant's ability to participate in the study

Serious illness requiring systemic treatment and/or hospitalization until participant either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 7 days prior to study entry

Requirement for any current medications that are prohibited with any study drugs

Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical illness

Any prior use of entecavir for treatment of hepatitis B for greater than 8 weeks while the participant was known to be HIV infected

Presence of decompensated cirrhosis

Pregnant or breastfeeding

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00811954